The Home Bacteritic and Biological Preparations for Correction of Dysbiosis

Miroshnik O.A.

Last years new points of view received spreading to the treatment, connected with restoration of natural ecology of organism and based on using of active biological products. One of aspects of such point of view is normalization of changing microbic view of the organism with the help of bacteritic and biopreparations.
At present time traditionally existing deficit of bacteritic and biopreparations on the whole is liquidated with the efforts of the new industrial and commercial structures. Moreover, besides such for a long time known preparations as bifidumbacterin, lactobacterin, colibacterin, and bificol, a great number of new remedies appear, among which doctors, pharmaceutists and patients orientate themselves difficulty. We hope that proposed in present publication systematization of bacteritic preparations intended for correction of biocenosis of mucous membranes, helps more prime and effective use all of its rich armoury in daily practice.

1.Bacteritic preparations - eubiotics

The most significant group of bacteritic preparations is represented by eubiotics - medical remedies, containing in the capacity as acting substance definite strains of representatives of microflora of healthy human organism. It is known that bacteria in norm populating mucous membranes, render antagonistic action in respect of pathogenic and conditional pathogenic microflora, provide vitamin forming and fermentative functions.

1.1 Preparations of bifidobacteria family
The most known and wide applying preparation-eubiotic - Befidumbacterin, contain bifidobacteria species of bifidum. Namely this species of bifidobacteria prevails in intestine of newborns and children of the first years of life and therefore bifidumbacterin is the basic preparation for correction of biocenosis of children intestine.
Indications for applying of bifidumbacterin is very wide, but the main of them are disfunctions of intestine in consequence of dysbacteriosis, acute intestine infections, applying with prophylactic aim in weakened children with anemia, rachitis, diathesis and by early transference of children from breast on artificial feeding and etcetera. Four main forms of Bifidumbacterin exist: bottle, ampule, tablet and powder in packets from laminiran foil.
The series of advantages have the form of Bifidumbacterin in powder of JSC "Partner" production, which represents itself mixture of dry bifidumbacteria with chemically clean lactose, packed in gas-proof packets from laminiran aluminium foil. Production technology of this preparation envisages moving off medium of cultivation and practically prime absence (less 10 %) dead bacterial cells. Therefore by preparation dissolution forms itself almost colourless opalescent suspension with out expressed smell and taste. Lactose, promoting the growth of bifidumbacteria in intestine, increases slightly the time of preparation dissolution.
Bifidumbacterin-forte is a complex bacteritic preparation, containing immobilized on ossiculum activated charcoal of bifidobacteria species of bifidum. In contact with mucous membrane of intestine sorbent gives the possibility of bifidobacteria species of separate microcolonies. Preparation possesses all the bifidumbacterin properties and simultaneously antitoxic action belonging to sorbent. Preparation renders more expressed clinical effect is capable to normalize disturbed biocenosis of intestine in earlier frists in comparison with usual bifidumbacterin. The preparation may apply after taking food and does not demand obligatory preliminarily dissolution in water.
Bifidumbacterin in suppositories uses for treatment of intestinal dysfunction with injury of its distal sections (colitis, proctitis) and gynecological practice (senile nonspecific bacterial colpitis, bacterial vaginousis, injury of vagina cleanness of the 3 - 4 degrees, make ready of labor passages for delivery and etcetera).
Bifilis - is a combined preparation, containing bifidobacteria species of bifidum and lysozyme (in one bottle of 5 doses and 10 mg accordingly). Lysozyme possesses bifidogenic, immunomodulating, antiinflammatory, reparative and antimicrobic action. Optimal combination of bifidobacteria and lysozyme in present preparation permits to strengthen the medical action of each component.

1.2 Preparations of lactobacteria family
Lactobacteria together with bifidobacteria are also the main representatives of normal human microflora. Lactobacteria present in all sections of digestive tract, beginning with the oral cavity and finishing with the large intestine, are prevailing flora of genital tract, display in breast milk. The first attempts of medical lactobacteria applying for correction of biochemical processes proceeding in intestine, undertook by I. I. Mechnicov already 100 years ago. In following expressed antagonistic activity of lactobacteria was founded against putrefactive conditionally pathogenic microorganisms and stimuli of acute intestinal infection. Indicated activity is connected with capability of lactobacilli form the lactic acid, hydrogen peroxide, lysozyme and other substances with antimicrobic action to the wide spectrum of Gram-positive and Gram-negative bacteria. Reparative properties and immunomodulating role of lactobacteria are exposed, displaying, in particular, in capability to raise general level of secretory Ig A and titres of specific secretory antibodies, to strengthen phagocytes and other. Role of lactobacteria in lowering cholesterin level in blood is discussed. Prevention of cancerogenes production and destruction of oxalic acid preventing the formation of oxalates in organism is also discussed.
In our country preparation Lactobacterin is wide by used. Lactobacterin is created in the beginning of 70-th years on the basis of lactobacteria species of plantarum rendering so as bifidobacteria antagonistic action in respect of pathogenic and conditionally pathogenic microorganisms. Indications to its applying is similar with such as bifidumbacterin.
In composition of Acylact enter lactobacteria species of acidophilus. In contrast to lactobacteria species of plantarum, used for making ready of Acylact acidophilic lactobacteria belong to categories of obligate human microorganisms. Criterions for selection of new plant species of lactobacteria served capability of bacteria to acidoformation, antimicrobic activity, adgesive properties, promoting long preservation in intestine, steadiness to action of digestive secretions and applying of antibiotics. All of these conditions conform the new preparation Acylact. Acylact is applied on indication, general with other bacteritic preparations: dysbacterioses of intestine, acute intestinal infections, chronic enterocolitis and also inflammatory diseases of mucous membrane of oral cavity. So far as acylact is characterized with heightened acidoformation activity, it is preferable for treatment of dysbacteriosis in patients with hypoacidous states and deteriorative peristalsis of intestine.
Diminished contents of lactose in acylact, in combination with high capability making up the basis of preparation of acidophilic lactobacteria to break up lactose, makes acylact means of selection for treatment of dysbacteriosis of intestine in patients with intolerance of milk (lactose insufficiency). Acylact applying during 2-3 courses in children with atopic dermatitis brings to normalization of initially oppressed immunity and improvement of clinical symptomatic.
Acylact in suppositories uses for treatment of gynecological diseases, accompanied with disturbance of vaginal microflora. In norm vaginal microflora represents inself mainly with lactobacteria, the so called Dederleins bacilli, which support in vagina the acidic medium and suppress the growth of conditionally pathogenic microorganisms. Acylact in suppositories is applied by pathological states, being found up with deficit of lactoflora of female genital tracts which is particularly significant by following diseases:
1. Senile colpitis - degree of settlement of vagina's mucous with lactobacteria depend on estrogen production that is why in postmenopausal period by estrogenic in sufficiency, lactoflora's level deteriorates, with that development of row of symptoms of senile colpitis (dryness, mucous atrophy and other), and also growth of frequency of urine infections is connected;
2. Nonspecific bacterial colpitis caused with staphylococcus, colon bacillus or their association;
3. Steady disturbance of cleanness of vaginal secret till 3 - 4 degrees;
4. Bacterial vaginousis, which, as it is known, is characterized with growing of anaerobic flora and sharp impoverishment of vagina mucous with lactobacteria. In the present case acylact is included in complex therapy, foreseeing also applying of metronidazole or clindamycin.
5. Courses of continuous antibioticotherapy, suppressing of natural vaginal microflora.
6. Prophylactic of bacterial colpitis and cystitis by frequent changing of sexual partners.
7. In complex with other preparations by treatment of chlamidiosis, mycoplasmical infection of female genital tracts.
8. Preparation of labor passages to delivery, so far as formating from the first hours of newborn life biocenosis of intestine in many cases depends on microbic view of mother's labor passages.
Contraindication to acylact in suppositories prescription is candidiasis thus as in some cases quickly displacement pH in acidic side is capable to growth of fungi. Acylact in the present case is used after specifical antifungous therapy or after applying of Bifidumbacterin in suppositories.
Acylact is also turned out in tablets, applying of which by means of resorption in the mouth is shown with inflammatory diseases of gums and mucous of oral cavity.
Acipol is a combined preparation, consisting of acidophilic lactobacteria and inactivated Kefir grevis by means of warming up is turned out in tablets for 5 doses. The preparation distinguishes with high activity in respect of pathogenic and conditionally pathogenic microflora, normalizes some immunological indices. Acipol is indicated from the first days of child's life by acute intestine infections, dysbacteriosis, weakend patients with signs of exudative diathesis and other allergic manifestations.

1.3 Preparations of colibacteria family
Preparations of colibacteria family - Colibacterin is the first native bacteritic preparation. It contains antagonistic active strain of nonpathogenic colon bacillus M-17. Some specialists consider, that the present strain, educed already many years ago, at present time somewhat lost antagonistic activity, and capability to get accustomed to intestine. Colibacterin is applied on the whole by chronic diseases of large intestine in elderly people, in which microflora of the given section of intestine is mainly settled with colon bacilli, and also by dysbacteriosis, conditioned by present of hemolyzing form of colon bacillus.
Combined preparation Bificol contains bifidobacteria species of bifidum and colon bacillus of the strain M-17, consequently, its action and indication to applying in many cases is similar with such as Bifidumbacterin and Colibacterin.

Abroad not a few preparations-eubiotics is also turned out. However because of high cost attempts of their wide inculcation on the Russian pharmaceutical market up to now has no significant success.
Bifiform (Ferrosan) is turned out in capsule with gastro insoluble covering and contains bifidobacteria species of bifidum and enterococci.
Primadophilus (Nature's Way) is turned out in two forms. Powder for making ready of suspension contains bifidobacteria species of infantus and longum and lactobacilli species of acidophilus and rbanmosus. The present form is prescribed for children from the first days of life till 5 years. Preparation's variant in form of capsules additionally contains bifidobacteria species of brevis and is prescribed for children in the age from 6 till 12 years. Primadophilus differs from absence in its composition allergenic factors; capsules are more comfortable for taking in comparison with powders, which is preliminarily necessary to dissolve in water.
Probionic (Enrich) represents itself chewing tablets with pleasant strawberry taste containing bifidobacteria species of adolescentis, infantis, longum, and acidophilic lactobacteria. The representative preparations are certificated as food additions.

2. Preparations - probiotics

The other big class of biopreparations using for correction of dysbacteriosis and treatment diarrhea's diseases constitute probiotics. Probiotics are activators of growth of normal microflora and educe substances suppressing of reproduction of pathogenic microorganisms.

The most known probiotics, in structure of which enter clean spores of Bacillus subtilis of strain IP 5832. These preparations Bactisubtil (Aventis) and Flonivin BS (ISN Pharmaceuticals). In Russia the similar preparation under the name of Bactisporin is turned out in the Scientific Industrial Union (SIU) "Immunopreparation" in city Ufa. Difference of Bactisporin is that it contains the lyophilized living bacteria Bacillus subtilis of the strain number 3H. Bacilli spores germinate in vegetative form in small intestine. This process achieves maximum in ileocecal sphere.
By determinating of spores free itself ferments are capabiling of splitting of proteins, fats, carbohydrates, and also acidic medium is formed, preventing putrefaction's process and growth of pathogenic bacteria. Besides that, ferments cause immediate lysis of cell Proteus walls, colon bacillus, pathogenic staphylococcus. So far as the present strain of bacilli is received with artificial way and is not a physiological component of intestinal biocenosis, by prescription of preparation from spore forming microorganisms caution is recommended: applying them with short courses and weak effect from preceding use of the bacteritic preparations - eubiotics.
Much so physiologically action of Linex (Lek) preparation, containing in quality of actively acting substances of acidophilic lactobacteria, bifidobacteria species of infantis and faecal streptococci. Lactic acidic bacteria produce lactic, acetic and propionic acids. Creating by them in intestinal acidic medium is unfavourable for the growth of pathogenic microorganisms. Lactic acidic bacteria participate in resorption of monosaccharides, stabilize membranes of cells of intestinal epithelium and regulate absorbability of electrolytes. Representatives of normal microflora (bifidobacteria and faecal streptococci) promote by that the restoration of biocenosis of intestine.
Enterol (till 2001 year its producer was concern "Sanofi - Wintrop"), contains lyophilizing fungi Sacchoromyces boulardii. The preparation normalizes disturbing equilibrium of intestinal microflora, promote elaboration with lymphoid cells of intestinal mucous of secretory Ig A. Enterol is effective by diarrhea, stipulating by taking of antibiotics, including by pseudomembranous colitis, causing by clostridial spore forming microflora.
Hylac forte (Ludwig Merkle) is a liquid, containing sterile concentrate of exchange products of symbionts of intestinal flora, biosynthetic lactic acid, short chained volatile fatty acids and other components. The present biological products change acidity of intestine contents in acid side, create of unfavourable conditions for growth of pathogenic microorganisms and stimulate the growth of normal microflora, improve physiological functions of gastro-intestinal tract, promote regeneration of mucous, restore disturbed water - electrolytic balance in lumen of intestine. Hylac is indicated with intestinal disfunctions, and allergic diseases, connected with dysbacteriosis of intestine, for prophylactic of dysbacteriosis and acute intestinal infections, appearing by sharp change of climatic conditions (diarrhea of travellers) and other.
Lactulose - is a synthetic disaccharide, turning out under different firm's name (Dufalac, Normase, Lactofalk, Portolac and other), also may be concerned to probiotics. Lactulose does not undergo hydrolysis in small intestine and enters the colon in invariable kind, where creates natural nutrient medium for growth of lactic acid bacteria, in the result of which there lactic and short - chained fatty acids are formed, acidity is heightened and peristalsis of intestinal large section is strengthened. The preparation inhibits the growth of Salmonella in intestine, decreases the formation of nitrogen containing substances and prevents absorption of ammonia in large intestine. Lactulose is used by chronic constipations, salmonellosis, digestion disturbances, connected with putrifactive process in the result of alimentary poisoning in baby's children and children till 10 years, and also by hepatic encephalopathy.

3. Bacteriophages

For sanation of mucous membranes, dermatic integuments and wound surfaces from pathogenic till conditionally pathogenic bacteria specific bacteriophages is applied with success.Bacteriophages are viruses, stricing exclusively bacteria, concern to ecologically safe biological objects for men and may by used for dysbacteriosis treatment, acute intestinal infections, purulent skin infections at any age. Bacteriophages like other viruses are absolute intracellular parasites, their reproduction takes place in living cell.
Penetrated in bacterium through disposing on its surface phagospecific receptors, DNA phage, changes synthesizing cell's mechanisms, forcing bacterium to synthesize DNA and phages' proteins. On definite stage bacterium is destroied and from it goes out the new generation of daughter's bacteriophages. The important property of bacteriophages is their high specificity, they lyse electoraly bacteria not only definite species, but also their of separately serological groups. Bacteriophages find correctly and destroy only those bacteria, against which their action is directed, not effecting the normal microflora of the organism to say nothing of its own cells. Namely this accounts for absence of accessory effects and contraindications to bacteriophages applying that make especially attractive their use in pediatric practice.
Origin in bacteria antibiotic stability does not tell on their sensitiveness to bacteriophages therefore the latter are often active even in respect of polyresistant hospital microflora. However it is necessary to account bacteriophages specifity: each species of phage recognizes in quality of its target only those bacteria serotypes, which has definite phagospecific receptors. Therefore it is necessary to prescribe bacteriophages under the microbiological control of sensitiveness to them of the present stimulus.
Native enterprise turns out the large spectrum of medical bacteriophages: Staphylococcal, Streptococcal, Coly, Proteus, Pyocyanic, Clebciellosis, Typhoid, Dysenteric, Salmonellosis. There are their combined forms: Coly-proteus bacteriophage, Intesty-bacteriophage (contains phage Shigella Flexner serovariants 1, 2, 3, 4, 6 and Sonne, Salmonella (paratyphoid A, B, enterilitis, tiphimurium, cholera suis, oranienburg), enteropathogenic group of colon bacillus, Proteus vulgaris and mirabilis, staphylococci, bacillus pyocyaneus and pathogenic enterococci). Piobacteriophage combined (contains phages staphylococci, streptococci, pathogenic colon bacillus, proteus and bacillus pyocyaneus). Consonant, but all the another preparation Piobacteriophage polyvalent purified contains phages of staphylococci, streptococci, pathogenic colon bacillus, bacillus pyocyaneus, proteus, and clebciella pneumonia. The present preparation distinguishes higher degree of purification from bacterial metabolites that considerably improves its gustatory qualities and makes means of the first choice in children till 1 year. Bacteriophage clebciellosis polyvalent purified is active in respect of clebciella pneumonia, ozena, and rhinoscleroma. Bacteriophage is usually turned out in fluid form or in tablets, at present time also turning out of Piobacteriophage combined and Staphylococcic bacteriophages in liniment form is right.
For the present bacteriophages is found the most spreading in dysbacteriosis treatment of intestine, acute intestinal infections, enterocolitis, purulent - inflammatory diseases of throat and nose. However the field of their clinical applying is considerably wider and they may be used with success for treatment of surgical, urogenital, skin and other infections.
In abroad manual mention of phagotherapy is absent. But it is necessary take account what, the fact that, first of all phagotherapy - is a special direction in bacteriology, worked out by russian scientists, and, second, of all use of bacteritic preparations with medical purposes in abroad standards is generally extremely limited. By way of illustration in the USA practically all the bacteritic preparations take to category of food additions, and, consequently, don't include to standard medical programs. Bacteritic preparations obviously get into the sphere of interest of dietitians, having tasks, distinguished from proper medical. Perhaps, it is not exaggeration to say, that in Russia much greater scientific material and experiment of bacteritic preparations use in medicine was accumulated.

4. Immunoglobulins preparations

Principle new direction in therapy of dysbacteriosis and acute intestinal infections is connected with creation in our country original remedy Complex immunoglobulins preparation (CIP). This preparation contains human immune globulin of three classes: Ig A (15-25 %), Ig M (15-25 %) and Ig G (50-70 %). Immune globulin preparation distinguishes from all other immune globulin preparation, applying in Russia, high content of Ig A and Ig M, heightened concentration of antibodies to enteropathogenic bacteria of intestinal group (Shigella, Salmonella, Escherichias, Clebciella and others), high concentration of antibodies to rotaviruses, and also peroral way of applying.
Being record in composition of immune globulin preparation Ig M renders bactericidal effect on pathogenic microorganisms. Ig A hampers their fastening to epithelium of mucous membrane, reproduction and provides quick moving off from the intestine, Ig G neutralizes microbic toxins and viruses, promotes "sticking" of bacteria to macrophages with following of their phagocytosis. Besides withdrawal from organism pathogenic and conditionally pathogenic microorganisms, Complex immunoglobulins preparations promote the growth of normal intestinal microflora (bifidobacteria, lactobacteria, enterococci, non-pathogenic colon bacilli), heighten the working out secretory Ig A and normalize the changed indices of systemic immunity. Peroral method of taking Complex immunoglobulins preparation provides of entrance big doses of acting substance to the place of defeat with following lowering adsorption of pathogenic on epithelium cells of mucous membranes of intestine and local immunomodulating effect.
In the process of the large-scale comparative investigation is indicated that among of all sorts of schemes of treatment of acute intestinal infections in children namely therapy of complex immune globulin preparations give the most results, fixing the price of such parameters as duration of symptoms in intoxication and diarrhea syndrome, repeated sowing of stimuli, changing of intestinal biocenosis and dynamics of the main indices of immunity.

Positive influence of complex immune globulin preparations is marked by allergic dermatoses therapy. This is explained with heightening of secretory level Ig A, in the result of which the local resistance of mucous of gastro-intestinal tract is strengthened and withdrawal from intestine entering allergens with food.
The main indications to applying of complex immune globulin preparations are following diseases and pathological processes:
1. Intestinal dysbacteriosis in children and adults, conditioned with any factors (carried acute intestinal infections, continuous and irrational antibioticotherapy, chronic diseases, stress, immunodeficient states and so on).
2. Acute intestinal infections. Possibilities of receiving expressed therapeutical effect over 2-3 days after beginning of taking make, Complex immunoglobulin preparation means of choice by treatment of acute intestinal infections (including rotaviruses etiology) in children of the first year of life.
3. Chronic enterocolitis.
4. Complex therapy of allergic dermatoses, combining with intestinal disfunction.
5. Immunodeficient states with disturbances mainly in humoral section of immunity.
In scientific research Institute of epidemiology and microbiology named after G.N.Gabrichevsky combined preparation Kipferon in vaginal suppositories is worked out, in composition of which enter complex immune globulin preparations and recombinant interferon alpha 2b in the dose of 500.000 ME.

5. Food additions

For correction of intestinal microflora the special food additions are applied. Food additions contain food fibers, refering to carbohydrates, which don't undergo digestion substrates for large intestinal microflora.
To food fibers rendering of stimulating effect on intestinal microflora concern oligosaccharides, in particular fruitooligosaccharides, the most known representatives of which is inulin. The large quantity of inulin contains in root - crops of topinambur. On the Russian market there are a great number of food additions, containing of topinambur concentrate. Fruitooligosaccharides and, in particular, inulin importantly stimulates the growth of bifidobacteria in intestine, changes pH of large intestine in acid side, promotes formation in intestine short - chained fatty acid and other biological active substances, rendering favourable action on intestinal biocenosis.

Thus, doctors and patients have to-day enough choice of means for preservation and supporting equilibrium of normal microorganism microflora. The task consists of rational and directed their applying with regard for individual peculiarities of biocenosis in concrete patient, that depends on understanding of differences in action of separate preparations and clear notion of therapeutical aims, pursued by their prescription.